Correction: Multidrug Resistant Pulmonary Tuberculosis Treatment Regimens and Patient Outcomes: An Individual Patient Data Meta-analysis of 9,153 Patients

Abstract

Background: Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.Methods and Findings: Three recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase ). Conclusions:In this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment.

Treatment Outcomes for Patients with Multidrug-Resistant Tuberculosis in Post-Earthquake Port-au-Prince, Haiti

“…[19][20][21] In a recent individual patient data meta-analysis of 9,153 patients, the pooled treatment success was only 54% (95% CI = 53-55%). 22 In that study, treatment success was associated with use of later-generation quinolones, ethionamide, or prothionamide, use of four or more likely effective drugs in the initial intensive phase, and use of three or more likely effective drugs in the continuation phase. In addition, the greatest odds of success were seen in patients who had 7.0-8.5 months for the intensive phase and a total length of treatment of 24.6-27.5 months.…”

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

“…These restrictions come mainly from the already-cited individual patient data meta-analysis showing a higher risk of treatment failure and relapse in patients with such strains compared to susceptible strains [36]. Interestingly, a previous individual meta-analysis showed that the inclusion of ethionamide/prothionamide as well as a longer use of injectables in the regimen were associated with treatment success; clofazimine, now considered as an important companion drug, was found not to have significant activity [5]. Several issues arise from the manner in which such meta-analyses were performed, as these assess the efficacy of individual drugs, neglecting the regimen in which individual drugs were used.…”

“…The overall treatment success was 48%; 10% had treatment failure; and 28% were lost to follow-up [4]. The same year (2012), an analysis of individual patient data showed very similar results [5]. Toxicity, long duration, and high costs were identified as causes of poor outcomes [4].…”

18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography for Assessing Treatment Response of Pulmonary Multidrug-Resistant Tuberculosis

“…Multidrug-resistant tuberculosis (MDR-TB), which is caused by Mycobacterium tuberculosis strains that are resistant to both isoniazid and rifampin, is a large public health threat. The majority of MDR-TB cases have unsatisfactory outcomes; there is a treatment success rate of approximately 60% despite the use of second-line anti-TB drugs for 18–24 months [1,2]. Historically, MDR-TB treatment response is monitored by microbiological examination of sputum-negative culture conversion [3].…”